Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma
Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma
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DOI：
10.1016/j.jtho.2018.05.038
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发表时间：
2018-10-01
影响因子：
20.4
通讯作者：
Baas, Paul
中科院分区：
文献类型：
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作者：
Quispel-Janssen, Josine;van der Noort, Vincent;Baas, Paul
前言：恶性胸膜间皮瘤（MPM）的治疗选择有限，结局较差。已证明程序性死亡1/程序性死亡配体1（PD-L1）检查点抑制剂在几种癌症类型中有效。Nivolumab是一种针对程序性死亡1的完全人源化单克隆抗体，具有良好的毒性特征。在MPM中，免疫系统被认为起着重要作用。因此，我们测试了nivolumab在复发MPM.Methods：在这个单中心试验中，MPM患者接受nivolumab 3 mg/kg静脉内每2周。主要终点为12周时的疾病控制率。治疗前和治疗中的活检标本，以分析生物标志物的respons.Results：包括34例患者，8例（24%）在12周的部分反应，另有8个稳定的疾病导致疾病控制率在12周的47%。1例在18周时达到部分缓解。4例病情稳定患者，肿瘤稳定6个月以上。26例患者（76%）发生了任何级别的治疗相关不良事件，最常见的是疲劳（29%）和瘙痒（15%）。9例患者（26%）报告了3级和4级治疗相关不良事件，主要为肺炎、胃肠道疾病和实验室检查异常。1例治疗相关死亡是由于肺炎，很可能由合并胺碘酮治疗引起。PD-L1在9个样本（27%）中的肿瘤细胞上表达，但与outcome.Conclusions无关：单药nivolumab在间皮瘤预治疗患者中具有有意义的临床疗效和可管理的安全性。PD-L1表达不能预测该人群的缓解。(C)2018年国际肺癌研究协会。爱思唯尔公司出版这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Introduction: Malignant pleural mesothelioma (MPM) has limited treatment options and a poor outcome. Programmed death 1/programmed death ligand 1 (PD-L1) checkpoint inhibitors have proven efficacious in several cancer types. Nivolumab is a fully humanized monoclonal antibody against programmed death 1 with a favorable toxicity profile. In MPM, the immune system is considered to play an important role. We therefore tested nivolumab in recurrent MPM.Methods: In this single-center trial, patients with MPM received nivolumab 3 mg/kg intravenously every 2 weeks. Primary endpoint was the disease control rate at 12 weeks. Pre- and on-treatment biopsy specimens were obtained to analyze biomarkers for response.Results: Of the 34 patients included, 8 patients (24%) had a partial response at 12 weeks and another 8 had stable disease resulting in a disease control rate at 12 weeks of 47%. One reached a partial response at 18 weeks. In 4 patients with stable disease, the tumor remained stable for more than 6 months. Treatment-related adverse events of any grade occurred in 26 patients (76%), most commonly fatigue (29%) and pruritus (15%). Grades 3 and 4 treatment-related adverse events were reported in 9 patients (26%), with pneumonitis, gastrointestinal disorders, and laboratory disorders mostly seen. One treatment-related death was due to pneumonitis and probably initiated by concurrent amiodarone therapy. PD-L1 was expressed on tumor cells in nine samples (27%), but did not correlate with outcome.Conclusions: Single-agent nivolumab has meaningful clinical efficacy and a manageable safety profile in pre-treated patients with mesothelioma. PD-L1 expression does not predict for response in this population. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).